Planned neck dissection (ND) is often performed before or after patients with head and neck squamous cell carcinoma (HNSCC) undergo chemoradiotherapy (CRT) for locally advanced nodal metastases. Using PET-CT to detect persistent disease could decrease the number of NDs and possibly lead to improved patient outcomes.

Dr. Hisham Mohamed Mehanna

Efficacy of PET-CT–Guided Surveillance

The randomized, multicenter noninferiority PET-NECK trial was conducted to evaluate the efficacy and cost effectiveness of PET-CT–guided surveillance compared with planned ND in patients with HNSCC. Hisham Mohamed Mehanna, MD, PhD, of the University of Birmingham, United Kingdom, presented the results of this trial during the Clinical Science Symposium “New Evidence on the Role of Surgery and PET Scans after Primary Chemoradiotherapy” on Monday, June 1 (Abstract 6009). The trial was conducted over almost 5 years at 43 centers in the United Kingdom.

Eligible patients had a histologic diagnosis of oropharyngeal, laryngeal, oral, hypopharyngeal, or occult HNSCC with clinical and CT/MRI imaging evidence of nodal metastases (stage N2 [a, b, or c] or N3), an indication for curative concurrent CRT, and were suitable for ND. Patients were randomly selected 1:1 to PET-CT–guided active surveillance or the standard treatment of ND (Fig. 1). The coprimary endpoints were overall survival and cost effectiveness. Secondary measures included disease-specific survival, locoregional control, ND complication rates, and quality of life.A total of 564 patients were enrolled, 282 in each treatment arm, with a median follow-up of 36 months. Overall, 84.4% had oropharyngeal cancer, and 81.6% were men, with a median age of approximately 57 years. Of the 282 patients in the ND arm, 221 (78.4%) underwent ND; 63 had ND before CRT, and 152 had ND after CRT. A total of 276 patients (97.9%) in the surveillance arm received CRT, 270 (95.7%) had PET-CT imaging, and 54 (19.1%) underwent ND after CRT.

Fig. 1. PET-NECK Trial Schematic

Fig. 1. PET-NECK Trial Schematic

The hazard ratio for overall survival was 0.92 in favor of surveillance (95% CI [0.65, 1.32]; p = 0.004), indicating noninferiority. There were no differences in mortality resulting from HNSCC or non-HNSCC causes. Two-year locoregional control rates (92.6% ND, 91.9% PET-CT), 2-year recurrence-free rates (84.0% ND, 85.6% PET-CT), ND complication rates (0.38 ND, 95% CI [0.30, 0.47], 0.42 PET-CT, 95% CI [0.24, 0.59]), and quality of life at 2 years were similar between the groups. A significantly greater number of severe adverse events occurred in patients in the ND group compared with the surveillance group (169 vs. 113 events; p = 0.001), a difference primarily driven by CRT, not ND. “We recommend that PET-CT–guided surveillance become the standard of care compared to planned neck dissection going forward,” Dr. Mehanna said.

Dr. Alison Florence Smith

Cost-Effectiveness Analysis

On behalf of the PET-NECK Trial Group, Alison Florence Smith, MSc, of the University of Leeds, United Kingdom, presented results from a 2-year cost effectiveness within-trial analysis and a decision model analysis of lifetime cost effectiveness (Abstract 6010). Secondary care activity was recorded on case report forms and the EQ-5D questionnaire was collected at baseline, treatment, and at 3, 6, 12, and 24 months. Resource use forms were collected for a subset of 42 patients and 35 caregivers. Cost-effectiveness analyses used the National Institute for Health and Care Excellence £20,000 ($30,398) per quality-adjusted life-years (QALY) willingness-to-pay threshold. The key treatment effect parameter in the lifetime model was the relative risk of recurrence in each arm, derived using data obtained in the PET-NECK trial.

Over the 2-year period, PET-CT surveillance had a per-person cost savings of £1,415 ($2,150) (95% CI [−£607, −£2218]) and a health gain of 0.07 QALYs (95% CI [−0.04, 0.19]) compared with ND. PET-CT surveillance was associated with a 99% probability of being cost saving, a 91% probability of being more effective, and a 99% probability of being cost effective when compared with ND at a £20,000 per QALY threshold. A sensitivity analysis was conducted that included primary care and community health care costs. In this analysis, the PET-CT cost savings increased to £5,791 ($8,802) (95% CI [−6,608, −4,970]).

PET-CT surveillance was not cost effective in the lifetime model, as the cost savings decreased to £990 ($1,505) (95% CI [−3,853, 1,858]) and PET-CT surveillance was less effective with a QALY of −0.05 (95% CI [−0.90, 0.80]). When compared with ND at a £20,000 per QALY threshold, the lifetime analysis results showed that PET-CT surveillance has an 86% probability of being cost saving, a 45% probability of being more effective, and a 50% probability of being cost effective. In her summary, Ms. Smith noted that a great deal of uncertainty surrounds the long-term data because the lifetime decision model is substantially extrapolated beyond the 2-year trial period.

A New Standard of Care?

The session concluded with a presentation by Discussant John N. Waldron, MD, of the University of Toronto, Canada. Regarding the conclusion that the PET-CT surveillance arm lost its cost effectiveness in the lifetime model, Dr. Waldron emphasized that a key assumption in the model was that there would be more recurrence in the PET-CT surveillance arm. “My view is that we cannot conclude this from the available data,” Dr. Waldron said.

When reviewing published response-driven neck management studies with the data from PET-NECK, the neck dissection rates are 20% or less and isolated neck failures are 4% or less. Improvements in outcomes are not only driven by improved imaging, specific node targeting, better quality assurance, new systemic agents, and improvements in surgical approaches, but also by the changing biology of the disease. For example, significantly better outcomes are being obtained with CT response–driven neck management in patients with HNSCC who test positive for HPV.

“These important data combined with large contemporary institutional series reporting excellent outcomes with response-based neck management strongly suggest response-based neck management should be the standard of care for patients with N2/3 selected to undergo radiation plus or minus chemotherapy,” Dr. Waldron said.